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(Stroke. 2000;31:1953.)
© 2000 American Heart Association, Inc.

Original Contributions

Dehydroepiandrosterone Sulfate Is Neuroprotective in a Reversible Spinal Cord Ischemia Model

Possible Involvement of GABA_A Receptors

Paul A. Lapchak, PhD; Deborah F. Chapman, MSc; Sonia Y. Nunez, BA Justin A. Zivin, MD, PhD

From the University of California San Diego, Department of Neuroscience, La Jolla, Calif.

Correspondence to Dr Paul A. Lapchak, University of California San Diego, Department of Neuroscience, MTF 316, 9500 Gilman Dr, La Jolla, CA 92093-0624. E-mail plapchak{at}ucsd.edu

Background and Purpose—Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) may function as neurotrophic or neuroprotective factors to protect central nervous system (CNS) neurons against a variety of insults, including excitotoxicity. The present study evaluated the pharmacological effects of DHEAS in a reversible spinal cord ischemia model.

Methods—DHEAS was administered (50 mg/kg IV) 5 or 30 minutes after the start of occlusion to groups of rabbits exposed to ischemia induced by temporary (15 to 60 minutes) occlusion of the infrarenal aorta. The group P₅₀ represents the duration of ischemia (in minutes) associated with 50% probability of resultant permanent paraplegia.

Results—The P₅₀ of the vehicle-treated control group, when behavioral analysis was assessed 18 hours after aortal occlusion, was 28.8±2.0 minutes. Neuroprotection was demonstrated if a drug significantly prolonged the P₅₀ compared with the vehicle-treated control group. Treatment with DHEAS at 5 minutes significantly (P<0.05) prolonged the P₅₀ of the group to 36.8±3.9 minutes. In addition, the DHEAS effect appeared durable, because a significant difference between the control and DHEAS-treated groups was still measurable at the 4-day time point. At 4 days, the P₅₀ of the control group was 26.1±2.2 minutes, whereas the P₅₀ for the DHEAS-treated group was 38.6±5.9 minutes. DHEAS was not neuroprotective if administered 30 minutes after occlusion. In addition, the GABA_A antagonist bicuculline abolished the neuroprotective effect of DHEAS.

Conclusions—The present study suggests that neurosteroids may have substantial therapeutic benefit for the treatment of ischemic stroke.

Editorial Comment

Possible Involvement of GABA_A Receptors

Chung Y. Hsu, MD, PhD, Guest Editor

Department of Neurology Washington University School of Medicine St Louis, Missouri

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